Linked Life Data

12364468

Source:http://linkedlifedata.com/resource/pubmed/id/12364468

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-10-4
pubmed:abstractText
Activin is a member of the TGF beta family of cytokines involved in the control of cell proliferation. We have previously shown that the majority of clinically nonfunctioning pituitary tumors do not respond to activin-induced growth suppression. Human pituitary tumors specifically express alternatively spliced activin type I receptor Alk4 mRNAs, producing C-terminus truncated isoforms designated Alk4-2, 4-3, and 4-4. However, it is not known whether these truncated activin receptors suppress activin effects on cell proliferation in human pituitary cells. Therefore, we investigated activin signaling in a human pituitary tumor cell line, HP75, derived from a clinically nonfunctioning pituitary tumor. HP75 cells express activin A mRNA and secrete activin A, as measured by ELISA and a functional bioassay. TGF beta administration decreases the proliferation of HP75 cells, suggesting that the signaling pathway shared by TGF beta and activin is functional in this cell line. However, activin neither inhibits cell proliferation nor stimulates reporter gene expression in HP75 cells, indicating that activin signaling is specifically blocked at the receptor level. HP75 cells express all truncated activin type I receptor Alk4 isoforms, as determined by RT-PCR. Because truncated Alk4 receptor isoforms inhibit activin signaling by competing with the wild-type receptor for binding to activin type II receptors, we hypothesized that overexpression of wild-type activin type I receptor will restore activin signaling. In HP75 cells, cotransfection of the wild-type activin type I receptor Alk4-1 expression vector increases activin-responsive reporter activity. Furthermore, transfection with wild-type activin receptor type I results in activin-mediated suppression of cell proliferation. These data indicate that truncated Alk4 isoforms interfere with activin signaling pathways and thereby may contribute to uncontrolled cell growth. Overexpression of the wild-type Alk4-1 receptor restores responsiveness to activin in human pituitary tumor-derived cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4741-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12364468-Activin Receptors, Type I, pubmed-meshheading:12364468-Activins, pubmed-meshheading:12364468-Alternative Splicing, pubmed-meshheading:12364468-Animals, pubmed-meshheading:12364468-Cell Division, pubmed-meshheading:12364468-Cell Line, pubmed-meshheading:12364468-DNA, pubmed-meshheading:12364468-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:12364468-Gene Expression, pubmed-meshheading:12364468-Humans, pubmed-meshheading:12364468-Luciferases, pubmed-meshheading:12364468-Mink, pubmed-meshheading:12364468-Phosphorylation, pubmed-meshheading:12364468-Pituitary Neoplasms, pubmed-meshheading:12364468-Protein Isoforms, pubmed-meshheading:12364468-Proteins, pubmed-meshheading:12364468-RNA, Messenger, pubmed-meshheading:12364468-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12364468-Signal Transduction, pubmed-meshheading:12364468-Transfection, pubmed-meshheading:12364468-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Overexpression of wild-type activin receptor alk4-1 restores activin antiproliferative effects in human pituitary tumor cells.
pubmed:affiliation
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't